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Association of Cortical and Subcortical β-Amyloid With Standardized Measures of Depressive and Anxiety Symptoms in Adults Without Dementia

. 2021 Winter ; 33 (1) : 64-71. [epub] 20201022

Language English Country United States Media print-electronic

Document type Journal Article

Grant support
K01 MH068351 NIMH NIH HHS - United States
R01 AG041851 NIA NIH HHS - United States
R01 AG056366 NIA NIH HHS - United States
R01 AG034676 NIA NIH HHS - United States
P50 AG016574 NIA NIH HHS - United States
R01 AG011378 NIA NIH HHS - United States
R33 AG058738 NIA NIH HHS - United States
R01 AG057708 NIA NIH HHS - United States
R37 AG011378 NIA NIH HHS - United States
U01 AG006786 NIA NIH HHS - United States
R01 NS097495 NINDS NIH HHS - United States
P30 AG062677 NIA NIH HHS - United States

OBJECTIVE: The purpose of this study was to test the hypothesis that subcortical β-amyloid (Aβ) deposition was associated with elevated scores on standardized measures of depressive and anxiety symptoms when compared with cortical (Aβ) deposition in persons without dementia. METHODS: The authors performed a cross-sectional study, derived from the population-based Mayo Clinic Study of Aging, comprising participants aged ≥70 years (N=1,022; 55% males; 28% apolipoprotein E [APOE] ε4 carriers; without cognitive impairment, N=842; mild cognitive impairment; N=180). To assess Aβ deposition in cortical and subcortical (the amygdala, striatum, and thalamus) regions, participants underwent Pittsburgh Compound B positron emission tomography (PiB-PET) and completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). The investigators ran linear regression models to examine the association between PiB-PET standardized uptake value ratios (SUVRs) in the neocortex and subcortical regions and depressive and anxiety symptoms (BDI-II and BAI total scores). Models were adjusted for age, sex, education level, and APOE ε4 carrier status and stratified by cognitive status (without cognitive impairment, mild cognitive impairment). RESULTS: Cortical PiB-PET SUVRs were associated with depressive symptoms (β=0.57 [SE=0.13], p<0.001) and anxiety symptoms (β=0.34 [SE=0.13], p=0.011). PiB-PET SUVRs in the amygdala were associated only with depressive symptoms (β=0.80 [SE=0.26], p=0.002). PiB-PET SUVRs in the striatum and thalamus were associated with depressive symptoms (striatum: β=0.69 [SE=0.18], p<0.001; thalamus: β=0.61 [SE=0.24], p=0.011) and anxiety symptoms (striatum: β=0.56 [SE=0.18], p=0.002; thalamus: β=0.65 [SE=0.24], p=0.008). In the mild cognitive impairment subsample, Aβ deposition, regardless of neuroanatomic location, was associated with depressive symptoms but not anxiety symptoms. CONCLUSIONS: Elevated amyloid deposition in cortical and subcortical brain regions was associated with higher depressive and anxiety symptoms, although these findings did not significantly differ by cortical versus subcortical Aβ deposition. This cross-sectional observation needs to be confirmed by a longitudinal study.

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Lyketsos CG, Lopez O, Jones B, et al.: Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002; 288: 1475–1483 PubMed

Geda YE, Schneider LS, Gitlin LN, et al.: Neuropsychiatric symptoms in Alzheimer’s disease: past progress and anticipation of the future. Alzheimers Dement 2013; 9:602–608 PubMed PMC

Craig D, Mirakhur A, Hart DJ, et al.: A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2005; 13:460–468 PubMed

Geda YE, Roberts RO, Knopman DS, et al.: Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Arch Gen Psychiatry 2008; 65:1193–1198 PubMed PMC

Apostolova LG, Cummings JL: Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature. Dement Geriatr Cogn Disord 2008; 25:115–126 PubMed

Brodaty H, Heffernan M, Draper B, et al.: Neuropsychiatric symptoms in older people with and without cognitive impairment. J Alzheimers Dis 2012; 31:411–420 PubMed

Geda YE, Roberts RO, Mielke MM, et al.: Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. Am J Psychiatry 2014; 171:572–581 PubMed PMC

Rosenberg PB, Mielke MM, Appleby BS, et al.: The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. Am J Geriatr Psychiatry 2013; 21:685–695 PubMed PMC

Pink A, Stokin GB, Bartley MM, et al.: Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: a population-based study. Neurology 2015; 84:935–943 PubMed PMC

Bensamoun D, Guignard R, Furst AJ, et al.: Associations between neuropsychiatric symptoms and cerebral amyloid deposition in cognitively impaired elderly people. J Alzheimers Dis 2016; 49: 387–398 PubMed

Johansson M, Stomrud E, Lindberg O, et al.: Apathy and anxiety are early markers of Alzheimer’s disease. Neurobiol Aging 2020; 85:74–82 PubMed

Lavretsky H, Siddarth P, Kepe V, et al.: Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults. Am J Geriatr Psychiatry 2009; 17:493–502 PubMed PMC

Krell-Roesch J, Lowe VJ, Neureiter J, et al.: Depressive and anxiety symptoms and cortical amyloid deposition among cognitively normal elderly persons: the Mayo Clinic Study of Aging. Int Psychogeriatr 2018; 30:245–251 PubMed PMC

Krell-Roesch J, Vassilaki M, Mielke MM, et al.: Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging. Transl Psychiatry 2019; 9:123. PubMed PMC

Chung JK, Plitman E, Nakajima S, et al.: Cortical amyloid β deposition and current depressive symptoms in Alzheimer disease and mild cognitive impairment. J Geriatr Psychiatry Neurol 2016; 29:149–159 PubMed PMC

Chung JK, Plitman E, Nakajima S, et al.: Lifetime history of depression predicts increased amyloid-β accumulation in patients with mild cognitive impairment. J Alzheimers Dis 2016; 49: 1189–1190 PubMed

Grothe MJ, Barthel H, Sepulcre J, et al.: In vivo staging of regional amyloid deposition. Neurology 2017; 89:2031–2038 PubMed PMC

Palmqvist S, Schöll M, Strandberg O, et al.: Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat Commun 2017; 8:1214. PubMed PMC

Hanseeuw BJ, Jonas V, Jackson J, et al.: Association of anxiety with subcortical amyloidosis in cognitively normal older adults. Mol Psychiatry (Epub ahead of print, August 16, 2018) PubMed PMC

Benarroch EE: The amygdala: functional organization and involvement in neurologic disorders. Neurology 2015; 84:313–324 PubMed

LeDoux J: The amygdala. Curr Biol 2007; 17:R868–R874 PubMed

LeDoux JE: Emotion circuits in the brain. Annu Rev Neurosci 2000; 23:155–184 PubMed

Roberts RO, Geda YE, Knopman DS, et al.: The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 2008; 30:58–69 PubMed PMC

Kokmen E, Smith GE, Petersen RC, et al.: The Short Test of Mental Status: correlations with standardized psychometric testing. Arch Neurol 1991; 48:725–728 PubMed

Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993; 43:2412–2414 PubMed

Rey A: L’examen clinique en psychologie. Paris, Presses Universitaires de France, 1964

Wechsler D: Wechsler Memory Scale-Revised. New York, Psychological Corporation, 1987

Kaplan E, Goodglass H, Weintraub S: Boston Naming Test. Philadelphia, Lippincott Williams & Wilkins, 2001

Lucas JA, Ivnik RJ, Smith GE, et al.: Mayo’s older Americans normative studies: category fluency norms. J Clin Exp Neuropsychol 1998; 20:194–200 PubMed

Wechsler D: Wechsler Adult Intelligence Scale-Revised. New York, Psychological Corporation, 1981

Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 1958; 8:271–276

Ivnik R, Malec J, Smith G, et al.: Mayo’s Older Americans Normative Studies: WAIS-R, WMS-R, and AVLT norms for ages 56 through 97. Clin Neuropsychol 1992; 6:83–104

Petersen RC: Mild cognitive impairment as a diagnostic entity. J Intern Med 2004; 256:183–194 PubMed

Winblad B, Palmer K, Kivipelto M, et al.: Mild cognitive impairment: beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004; 256:240–246 PubMed

Jack CR Jr, Wiste HJ, Weigand SD, et al.: Defining imaging biomarker cut points for brain aging and Alzheimer’s disease. Alzheimers Dement 2017; 13:205–216 PubMed PMC

Lowe VJ, Kemp BJ, Jack CR Jr, et al.: Comparison of 18F-FDG and PiB PET in cognitive impairment. J Nucl Med 2009; 50:878–886 PubMed PMC

Beck AT, Steer RA, Brown GK: Manual for Beck Depression Inventory-II (BDI-II). San Antonio, Tex, Psychology Corporation, 2001

Beck AT, Steer RA: BAI, Beck Anxiety Inventory: Manual. San Antonio, Tex, Psychological Corporation, 1990

Goukasian N, Hwang KS, Romero T, et al.: Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study. BMJ Open 2019; 9:e031947 PubMed PMC

Harrington KD, Gould E, Lim YY, et al.: Amyloid burden and incident depressive symptoms in cognitively normal older adults. Int J Geriatr Psychiatry 2017; 32:455–463 PubMed

Lussier FZ, Pascoal TA, Chamoun M, et al.: Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals. Alzheimers Dement 2020; 16:192–199 PubMed PMC

Donovan NJ, Locascio JJ, Marshall GA et al.: Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults. Am J Psychiatry 2018; 175: 530–537 PubMed PMC

Wu KY, Hsiao IT, Chen CS, et al.: Increased brain amyloid deposition in patients with a lifetime history of major depression: evidenced on 18F-florbetapir (AV-45/amyvid) positron emission tomography. Eur J Nucl Med Mol Imaging 2014; 41:714–722 PubMed

Harrington KD, Lim YY, Gould E, et al.: Amyloid-beta and depression in healthy older adults: a systematic review. Aust N Z J Psychiatry 2015; 49:36–46 PubMed

Madsen K, Hasselbalch BJ, Frederiksen KS, et al.: Lack of association between prior depressive episodes and cerebral [11C]PiB binding. Neurobiol Aging 2012; 33:2334–2342 PubMed

Perin S, Harrington KD, Lim YY, et al.: Amyloid burden and incident depressive symptoms in preclinical Alzheimer’s disease. J Affect Disord 2018; 229:269–274 PubMed

Donovan NJ, Hsu DC, Dagley AS, et al.: Depressive symptoms and biomarkers of Alzheimer’s disease in cognitively normal older adults. J Alzheimers Dis 2015; 46:63–73 PubMed PMC

Thal DR, Rüb U, Orantes M, et al.: Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 2002; 58:1791–1800 PubMed

Beach TG, Sue LI, Walker DG, et al.: Striatal amyloid plaque density predicts Braak neurofibrillary stage and clinicopathological Alzheimer’s disease: implications for amyloid imaging. J Alzheimers Dis 2012; 28:869–876 PubMed PMC

Jack CR Jr: Alzheimer disease, biomarkers, and clinical symptoms: quo vadis? Reply. JAMA Neurol 2020; 77:394 PubMed

Santos CY, Snyder PJ, Wu WC, et al.: Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: a review and synthesis. Alzheimers Dement (Amst) 2017; 7:69–87 PubMed PMC

Vemuri P, Lesnick TG, Przybelski SA, et al.: Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly. Brain 2015; 138:761–771 PubMed PMC

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